Inefficient processing of an olfactomedin-deficient myocilin mutant: potential physiological relevance to glaucoma

Biochem Biophys Res Commun. 2001 Apr 6;282(3):662-70. doi: 10.1006/bbrc.2001.4624.


Mutations in TIGR/MYOC (myocilin), a secretory protein of unknown function, have been recently linked to glaucoma. Most known mutations map to the C-terminus, an olfactomedin-like domain. We have previously shown that, in contrast to the wild-type, a truncated form of myocilin lacking the olfactomedin domain is not secreted. In this study, we present evidence that the mutant protein is not correctly processed in the endoplasmic reticulum (ER) and accumulates into insoluble aggregates. In addition, we show that the presence of increasing amounts of mutant protein induces a fraction of the soluble, native myocilin to move to the insoluble fraction. Given the importance of such protein aggregates in the etiology of several aging-related diseases, we propose that olfactomedin-defective mutants might contribute to the pathology of glaucoma through a mechanism involving intracellular accumulation of misfolded proteins.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoviridae
  • Cells, Cultured
  • Cytoskeletal Proteins
  • Detergents
  • Extracellular Matrix Proteins / chemistry
  • Extracellular Matrix Proteins / deficiency*
  • Extracellular Matrix Proteins / genetics
  • Eye Proteins / chemistry
  • Eye Proteins / genetics*
  • Eye Proteins / metabolism*
  • Genetic Vectors
  • Glaucoma / etiology*
  • Glaucoma / metabolism
  • Glycoproteins / chemistry
  • Glycoproteins / deficiency*
  • Glycoproteins / genetics*
  • Glycoproteins / metabolism*
  • Humans
  • Mutation*
  • Protein Folding
  • Protein Processing, Post-Translational
  • Protein Structure, Tertiary
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sequence Deletion
  • Solubility
  • Trabecular Meshwork / metabolism
  • Transfection


  • Cytoskeletal Proteins
  • Detergents
  • Extracellular Matrix Proteins
  • Eye Proteins
  • Glycoproteins
  • Recombinant Proteins
  • olfactomedin
  • trabecular meshwork-induced glucocorticoid response protein